Chiral organolithium complexes: The effect of ligand structure on the enantioselective deprotonation of Boc-pyrrolidine

The efficacies of a number of s-BuLi/chiral ligand complexes as reagents for the asymmetric deprotonation of Boc-pyrrolidine (1) to provide enantioenriched 2-lithio-Boc-pyrrolidine (2) have been evaluated by the conversion of 2 to 2-(trimethylsilyl)-Boc-pyrrolidine (3). The syntheses of new enantioenriched proline-based and bispidine ligands are described. The most effective newly examined ligands are the diproline-based diamino alcohol 20 and the alpha-methylbenzylamine-derived bispidine 35, which provided (S)-3 and (R)-3 with enantiomeric excesses of 72% and 75%, respectively. Use of the ligand (-)-isosparteine (28) resulted in lower conversions and enantioselectivities than (-)-sparteine (27). A rationale is proposed to explain the relative rates of the lithiation of 1 by s-BuLi/TMEDA, 27, or 28 complexes and the remarkable effectiveness of(-)-sparteine as the best chiral ligand examined to date.